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Characterization of epidermal growth factor receptor function in Lysophosphatidic acid signaling in PC12 cells
Author(s) -
Kim Shi Nae,
Park JungGyu,
Lee Eunhee Bae,
Kim Soung Soo,
Yoo Young Sook
Publication year - 2000
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(20000301)76:3<386::aid-jcb6>3.0.co;2-9
Subject(s) - lysophosphatidic acid , microbiology and biotechnology , epidermal growth factor , signal transduction , biology , mapk/erk pathway , neurite , receptor , chemistry , biochemistry , in vitro
Lysophosphatidic acid (LPA) is a lipid metabolite that induces the activation of mitogen‐activated protein kinase (MAPK) through binding to the G protein‐coupled receptor in a number of cell lines and cultures. Recent studies have revealed that LPA is able to rapidly induce the phosphorylation of MAPK through an epidermal growth factor (EGF) receptor‐dependent pathway. We investigated the role of the EGF receptor in the signaling pathway initiated by LPA stimulation in nerve growth factor (NGF)‐responsive PC12 cells well known to transiently retract their own neurites upon LPA stimulation. LPA‐stimulated MAPK signaling was suppressed by the selective EGF receptor inhibitor and in the dominant negative mutant EGF receptor cell line. As in the EGF signaling pathway, the complex of EGF receptor with adapter proteins Shc and Sos was formed in response to LPA stimulation, suggesting there is an intracellular mechanism for transactivation. A neurite retraction assay was also performed to examine the role of the EGF receptor in PC12 cell differentiation, which related to the involvement of LPA‐induced neurite retraction. These results suggest that the receptor tyrosine kinase can be activated in a ligand‐independent manner through intracellular crosstalk between the signaling pathways. J. Cell. Biochem. 76:386–393, 2000. © 2000 Wiley‐Liss, Inc.